Molecular characterization of an HIV-1 drug target and antiviral compound development

• Main Author: Maselko, Maciej
• Other Authors: Pastey, Manoj
• Language: en_US
• Published: 2011
• Subjects: HIV-1; Microbicide; Antiviral
• Online Access: http://hdl.handle.net/1957/21160

The Human Immunodeficiency Virus -1 (HIV-1) has been the source of substantial human misery since it was first discovered in the early 1980s. Despite remarkable progress that has been made towards understanding HIV- 1, there is no cure, no vaccine and life-prolonging therapies are beyond the reach of millions in need. Our research sought to both gain insight into potential therapeutic targets as well as the preclinical testing of drug candidates. We demonstrate that a RhoA derived peptide is an effective inhibitor of HIV-1 entry. Although this peptide inhibits HIV-1 due to its poly-anionic nature, it nevertheless demonstrates that endogenous host proteins may be repurposed for novel therapeutic uses. We also characterized the mechanism and effectiveness of Basant, a polyherbal topical microbicide candidate for the prevention of HIV-1 transmission. Our data demonstrate that it inhibits the entry of both CCR5 and CXCR4 tropic HIV-1 at non-toxic concentrations. Finally, data is presented on the characterization of a novel HIV-1 protein expressed from an alternative reading frame of the HIV-1 polymerase gene. We demonstrate that this protein is localized to the nucleolus and is likely expressed from a novel HIV-1 transcript. This work lays the foundation for further studies to target this protein for drug development. === Graduation date: 2011 === Access restricted to the OSU Community at author's request from May 9, 2011 - May 9, 2012